Drug metabolism problems such as production of toxic metabolites and unfavorable pharmacokinetics cause almost half of all drug candidate failures during clinical trials. Although glucuronidation is one of the most important routes of biotransformation, the broad, overlapping substrate specificity of the hepatic UDP-glucuronosyltransferases (UGTs) that catalyze glucuronidation remains poorly understood. To meet the strong market demand for improved preclinical metabolism assessment and enable more rapid, cost-effective drug design, PanVera will develop a system for structure-based prediction of xenobiotic glucuronidation. To accomplish this, a quantitative structure activity relationship (QSAR) approach will be used to delineate the key properties of chemicals that determine their suitability as substrates for individual UGT isozymes. Phase I studies will focus on developing molecular tools for elucidating UGT substrate specificity using UGT2B7 as a model. Phase II studies will employ these tools to develop QSAR models for the key hepatic UGT isozymes. Both Phase I and Phase II studies will result in valuable commercial products for drug discovery, including the HTS assay method developed in Phase I, and the QSAR database and predictive modeling software developed in Phase II. The goal is to revolutionize drug discovery by providing a computerized solution to one of the most serious bottlenecks in drug discovery. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE